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FASEB J. 2019 Jul;33(7):8202-8210. doi: 10.1096/fj.201802817R. Epub 2019 Apr 24.

Epithelial cell-derived prostaglandin D2 inhibits chronic allergic lung inflammation in mice.

Author information

1
Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
2
Department of Pathobiochemistry, Osaka University of Pharmaceutical Sciences, Osaka, Japan.
3
Laboratory of Chemical Pharmacology, Daiichi University of Pharmacy, Fukuoka, Japan.
4
Human Gene Sciences Center, Tokyo Medical and Dental University, Tokyo, Japan.

Abstract

The precise role of prostaglandin D (PGD)2 in allergic lung inflammation remains controversial. Here, we aimed to clarify the role of PGD2 in chronic allergic lung inflammation using hematopoietic PGD synthase (H-PGDS)-deficient mice. Repeated intranasal administration of ovalbumin (OVA) resulted in eosinophilic infiltration and mucin production in the lungs of wild type (WT) mice, leading to respiratory dysfunction. H-PGDS deficiency exacerbated these effects, which were accompanied by increased mRNA expression of TNF-α and eosinophil chemoattractants. The bronchial epithelium expressed both H-PGDS and TNF-α in the inflamed WT lung, and H-PGDS deficiency increased TNF-α expression further. In cultured bronchial tissue of WT mice, treatment with LPS elevated mRNA expression of TNF-α and eosinophil chemoattractants. H-PGDS deficiency promoted the expression of these factors, which was inhibited by treatment with PGD2 receptor, D prostanoid (DP) receptor agonist, or PGD2 metabolite 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2). Treatment with TNF-α receptor antibody inhibited eosinophil chemoattractant expression. In vivo, administration of DP agonist or 15d-PGJ2 inhibited OVA-induced allergic lung inflammation. Bronchial epithelial cell-derived PGD2 attenuated lung eosinophilic infiltration with chronic allergic inflammation; these phenomena are at least partly attributed to the inhibition of TNF-α production via DP activation or 15-deoxy-Δ12,14-PGJ2 signaling.-Maehara, T., Nakamura, T., Maeda, S., Aritake, K., Nakamura, M., Murata, T. Epithelial cell-derived prostaglandin D2 inhibits chronic allergic lung inflammation in mice.

KEYWORDS:

15d-PGJ; DP receptor; allergy; eosinophil

PMID:
31018708
DOI:
10.1096/fj.201802817R

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